Patients with cancer have blood leucocytes capable of in vitro destruction and/or inhibition of growth of cells derived from their own tumor or from tumors of a similar histological type. These same leucocytes do not affect cells from other types of tumors or from normal tissue. In the majority of tumor types studied, the presence or absence of these cytotoxic leucocytes has not correlated with the stage or extent of disease. However, studies performed with highly purified lymphocytes from patients with bladder carcinoma have shown a definite correlation between the presence of specifically cytotoxic lymphocytes and the stage of disease. We have developed a 3H- proline modified microcytotoxicity test (MCT) which more accurately detects lymphocyte mediated target cell destruction than does the standard Takasuki and Klein test which detects a combination of destructive and growth inhibitory effects. Using this modified test, we have found 53% (8/15) of bladder cancer patients with low stage disease to have specifically cytotoxic lymphocytes versus 17% (2/12) of patients with advanced stage disease. Only 2 of 49 control lymphocyte donors exhibited bladder specific reactivity. We propose here to expand our preliminary study utilizing the 3H-proline MCT to include a large number of patients with bladder carcinoma who will be tested serially for the presence of specific lymphocyte cytotoxicity with detailed clinical follow-up. This prospective study will enable us to determine if the presence in some patients of this specific cell- mediated immune response is an indication of host resistance and of prognostic significance. The effect of therapeutic modalities on this specific lymphocyte function will also be assessed. These studies will provide some additional insight into the immunobiology of bladder carcinoma and possibly provide criteria for patient management.